In 1966, Shik, Severin and Orlovskii discovered that electrical stimulation of a region at the junction between the midbrain and
hindbrain elicited controlled walking and running in the cat. The region was named Mesencephalic Locomotor Region (MLR). Since
then, this locomotor center was shown to control locomotion in various vertebrate species, including the lamprey, salamander, stingray,
rat, guinea-pig, rabbit or monkey. In human subjects asked to imagine they are walking, there is an increased activity in brainstem nuclei
corresponding to the MLR (i.e. pedunculopontine, cuneiform and subcuneiform nuclei). Clinicians are now stimulating (deep brain
stimulation) structures considered to be part of the MLR to alleviate locomotor symptoms of patients with Parkinson’s disease. However,
the anatomical constituents of the MLR still remain a matter of debate, especially relative to the pedunculopontine, cuneiform and subcuneiform
nuclei. Furthermore, recent studies in lampreys have revealed that the MLR is more complex than a simple relay in a serial descending
pathway activating the spinal locomotor circuits. It has multiple functions. Our goal is to review the current knowledge relative
to the anatomical constituents of the MLR, and its physiological role, from lamprey to man. We will discuss these results in the context of
the recent clinical studies involving stimulation of the MLR in patients with Parkinson’s disease.
Keywords: Locomotion, mesencephalic locomotor region, pedunculopontine nucleus, cuneiform nucleus, laterodorsal tegmental nucleus,
lamprey, acetylcholine, Parkinson’s disease.
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